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Biomedical subjects

P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 289 records · Page 16Linked to original sources
PubMed1985

Rapid diagnosis of cytomegalovirus infection.

Several assays are in preparation for the diagnosis of cytomegalovirus infection in acquired immune deficiency syndrome and other immunocompromised patients. In particular, ELISA and DNA probes look to be particularly promising for testing body fluids and tissue sections respectively but these assays are not currently available. The technique of detection of early fluorescent antigen foci (DEAFF) has for some time been available as a diagnostic service to immunocompromised patients served by the author's laboratory. Although it requires cell culture and immunofluorescent techniques it is capable of detecting most patients with productive infection. In particular, the rapid availability of results has allowed patients to be entered into trials of new antiviral agents.

Acquired Immunodeficiency Syndrome↗
PubMed1985

A seroepidemiological study of cytomegalovirus and Epstein-Barr virus in rheumatoid arthritis and sicca syndrome.

Antibodies to cytomegalovirus (CMV) and Epstein-Barr virus capsid antigen (EBVCA) were examined in 41 patients with rheumatoid arthritis (RA), 26 patients with primary sicca syndrome, and 26 healthy subjects of similar age and sex. IgG antibody titres to EBVCA and CMV were similar in all three groups, apart from a trivial increase of antibodies to EBVCA in RA. False positive IgM anti-CMV antibodies detected in serum from one patient with sicca syndrome and 20 patients with RA were shown to be due to rheumatoid factors. These data did not support recent suggestions that patients with these diseases showed exaggerated immunological responses to either virus and emphasised the need to incorporate adequate laboratory and disease controls when seroepidemiological studies are performed on sera containing rheumatoid factors and autoantibodies.

Adult↗
PubMed1984

Rapid diagnosis of cytomegalovirus infection in immunocompromised patients by detection of early antigen fluorescent foci.

Cell-cultures of cytomegalovirus (CMV) were fixed after 24 hours' incubation and examined by a monoclonal antibody based immunofluorescence method for the detection of CMV-specific early antigens. 385 urine, saliva, or blood samples from 63 immunocompromised patients were inoculated onto cell-cultures. Comparison with the results of conventional cell-cultures in patients who remained uninfected showed that the new technique had a specificity of 100%. The sensitivity was 80%. This immunofluorescence method gave positive results 27h after inoculation of the specimens instead of the mean of 17 X 5 days with the conventional method based on detection of cytopathic effect. 3 saliva samples, from patients who had previously excreted CMV, reacted in the immunofluorescence method but CMV, reacted in the cell-cultures-perhaps because the assay identified defective, interfering particles in these samples. The monoclonal antibodies were also used successfully in another immunofluorescence system to diagnose cytomegalovirus pneumonitis in 3 patients by testing material obtained by bronchoalveolar lavage.

Antibodies, Monoclonal↗
PubMed1984

A user's guide to the indirect solid-phase radioimmunoassay for the detection of cytomegalovirus-specific IgM antibodies.

In this review full laboratory details are given of a solid-phase indirect radioimmunoassay for the detection of specific IgM antibodies against cytomegalovirus. Practical advice is given on readily available commercial sources of reagents, a simple iodination procedure, the rapid dilution of sera under test and calculation of the results with a computer program available from the authors. Problems encountered with the assay are also detailed such as interference by rheumatoid factor, deterioration of the radiolabel and high background binding found with some sera. If these problems are avoided by the methods given in the text then the radioimmunoassay has been shown to give results of 100% specificity with 89% sensitivity for detecting congenital infection and 92% sensitivity for identifying primary cytomegalovirus infection in pregnant women.

Antibodies, Viral↗
PubMed1984

Intra-uterine transmission of cytomegalovirus in women known to be immune before conception.

A prospective study identified 785 pregnant women who had been shown to possess complement fixing antibodies against cytomegalovirus (CMV) during a previous pregnancy. As these women were thus known to have been immune prior to their subsequent conception, their neonates were examined for evidence of congenital CMV infection. Specimens were obtained from 725 (92%) of the neonates and congenital infection was found in only one (0.14%). The elder sister of the infected child was also shown, by retrospective testing of her stored cord serum for specific IgM antibodies, to have been infected in utero. Thus, one woman was identified who had delivered consecutive siblings congenitally infected with CMV. We conclude that some women have a propensity for intra-uterine transmission of CMV, despite being immune prior to conception, and speculate that such women may have acquired their infections perinatally.

Adult↗
PubMed1984

Antibody against viruses in maternal and cord sera: non-specific inhibitors are found to higher titre on the maternal side of the circulation.

Pregnancies were identified in which maternal IgG antibodies against rubella virus were not detectable by single radial haemolysis. Twenty paired maternal/cord sera were then tested for haemagglutination-inhibiting (HI) activity against rubella virus without kaolin pretreatment of the sera. In the absence of specific antibody, the HI activity observed could thus be ascribed to the effect of non-specific inhibitors. The HI activity in maternal sera was significantly (P less than 0.001) higher than that in cord sera. The 20 pairs of sera were similarly tested against a bunyavirus, an alphavirus and a flavivirus, both with and without kaolin pretreatment. The results showed non-specific inhibitors were found to higher titre in maternal sera, with the difference being statistically significant (P less than 0.001) for each of the three viruses.

Absorption↗
PubMed1984

A prospective study of primary cytomegalovirus infection during pregnancy: final report.

In a 7-year prospective study cytomegalovirus (CMV) was shown to infect approximately twice as many pregnant women as did rubella virus. Fetal loss occurred in 4/26 (15%) early CMV infections which was seven-fold higher than the rate found in controls (16/744; 2.2%). There was no evidence that fetal loss resulted from intrauterine transmission of virus. Fifty-eight women experienced primary CMV infection and congenital infection was found in nine (20%) of the 46 infants from whom clinical samples were obtained. Transmission of virus was found in 20%, 0% and 40% in the first, second and third trimesters respectively. All babies were normal at birth but two have so far developed definite intellectual impairment attributable to cytomegalovirus infection. The mothers of both of these cases were infected after the fetus had become legally viable. We conclude that the lessons learned from studying rubella infection during pregnancy cannot be applied to cytomegalovirus; in particular, we could find no evidence that termination of pregnancy should be offered to women with early CMV infections.

Abortion, Spontaneous↗
PubMed1984

Diagnostic techniques for cytomegalovirus infection.

The many methods used for identifying cytomegalovirus (CMV) infection in immunocompromised patients are discussed. In general, the diagnosis is best made by detecting virus rather than by looking for evidence of an immune response, since the ability of patients to respond immunologically is obviously impaired. Until recently the laboratory took two or three weeks to culture the virus, but more modern methods seem to be capable of providing the same service within 24 hours. These developments will allow infections to be diagnosed sufficiently early for the patients to be entered into trials of potential antiviral agents and for any therapeutic response to be monitored. These modern diagnostic methods are discussed, as is the usefulness of collecting clinical specimens from different anatomical areas as a way of distinguishing symptomatic CMV infection from viral shedding in a patient whose disease is not caused by CMV.

Antibodies, Viral↗
PubMed1983

Lead in neonates and mothers.

Blood lead was estimated in mothers post partum and infants at birth using the Jarrell-Ash 810 Atomic Absorption Spectrophotometer equipped with the Delves cup sampling system. 1665 pairs (mother and her infant) of blood samples were examined. The geometric mean for mothers and infants was 59.6 micrograms/l, SD = 25.2, and 40.7 micrograms/l, SD = 20.1, respectively. 3.5% of mothers had lower blood lead concentration than their infants. A significant correlation was observed between the blood lead concentration of infants and mothers, r = 0.8111, y = 0.6322x + 3.868 +/- 11.345. The haematocrit ratio was estimated in 1209 pairs. The geometric mean for mothers and infants was 0.3937, SD = 0.0402 and 0.5158, SD = 0.0499, respectively. No significant correlation was observed between the haematocrit ratio of infants and mothers. Similarly, no significant correlation was observed between the haematocrit ratio and blood lead concentration of mothers and infants. The examination of blood lead concentration for seasonal variation showed no significant increase in lead, although a significant drop in values was observed in spring and possible explanations offered.

Female↗
PubMed1983

Hotting-up the complement-fixation test.

A detailed investigation into the effect of modifying the incubation temperature of the complement-fixation (CF) test is described. For varicella-zoster virus cytomegalovirus and rubella virus, increasing the incubation temperature progressively increased the sensitivity of the CF test to reach a maximum at 15 degrees C, at which temperature the geometric mean titre of seropositive samples was significantly greater than that found at 4 degrees C. For these three viruses, each serum shown to contain IgG antibodies by ultrasensitive radioimmunoassay procedures was detected by CF following incubation at 15 degrees C. No false-positive reactions occurred at 15 degrees C, but it was our impression that anticomplementary activity was enhanced at this temperature. Significant increases in antibody titre at 15 degrees C were also seen when measles virus, respiratory syncytial virus, adenovirus and Mycoplasma pneumoniae were employed as CF antigens. The results demonstrate that the CF test should be performed at 15 degrees C if optimum sensitivity is to be achieved. The ability of the test to detect significant rises in antibody titre was not impaired at the higher incubation temperature.

Adenoviridae↗
PubMed1983

Antibody response to cytomegalovirus after renal transplantation: comparison of patients with primary and recurrent infections.

The specific antibody response of 22 renal transplant patients with primary cytomegalo-virus (CMV) infection was compared to that of 21 patients with recurrent infection using seven different techniques to measure antibody. With primary infection seroconversion occurred between two and 12 weeks postoperatively, and geometric mean titers increased rapidly during this interval with each test except virus neutralization. In the group with recurrent CMV infection, geometric mean titers declined slightly initially and then increased rapidly to reach peak levels by 10 weeks. In both primary and recurrent infections, IgM antibody was detectable by radioimmunoassay and indirect immunofluorescence; the former procedure was clearly the more sensitive. After absorption to remove rheumatoid factor, 20 of the 22 patients with primary infection and eight of the 21 with recurrent infection had IgM antibody to CMV by radioimmunoassay which often persisted for over six months. The former group had significantly more viremia and symptomatic infections than the latter. Two critically ill patients failed to develop IgM or neutralizing antibody.

Antibodies, Viral↗
PubMed1983

The consequences of primary cytomegalovirus infection in pregnancy.

Altogether 54 children exposed prenatally to maternal cytomegalovirus (CMV) infection were followed up in a prospective study. Nine had congenital infection with CMV and 37 escaped congenital infection; in 8 congenital CMV could not be confirmed. The birthweight of children with congenital CMV was significantly lower than that of both controls and those who escaped congenital infection. Intrauterine infection was not clinically suspected in any of the children with congenital CMV, although two had head circumferences less than the third centile. Subsequently one child with congenital CMV developed marked psychomotor retardation, and one, in whom congenital CMV was not confirmed, showed mild developmental delay. Speech and language ability was significantly impaired in children with congenital CMV compared with controls and those who escaped congenital infection, suggesting that subtle damage may have occurred. The incidence of intrauterine transmission of CMV after exposure to infection in the first trimester was 20% and in the third trimester 40%, but no congenital infections resulted from exposure in the second trimester. The severity of congenital infection was not related to the time of exposure in utero. Our findings suggest that the risk to an individual fetus from maternal infection in early gestation is so low that termination of pregnancy cannot be recommended; screening of women for primary CMV infection in pregnancy seems therefore to have limited value.

Birth Weight↗
PubMed1982

Specific IgM class antibody production following infection with cytomegalovirus.

Specific IgM class antibody production was studied in different groups of patients with characterized cytomegalovirus (CMV) infections using a radioimmunoassay (RIA). In pregnant women, IgM antibodies were detected only following primary infection and generally persisted less than 4 months. The demonstration of CMV-specific IgM during pregnancy is therefore diagnostic of recent primary CMV infection. In patients with symptomatic CMV infections, the appearance of IgM antibody was shown to be closely related to the onset of symptoms and coincided with production of complement fixing (CF) antibody. IgM antibodies were at maximum levels 3-4 weeks after presentation but generally declined to low or undetectable levels by 3-4 months. The significance of the results of testing for CMV-specific IgM in relation to clinical and other serological findings in these patients is discussed. IgM antibody production was also demonstrated in renal transplant patients with primary infections and in 6 of 21 recipients with secondary infections. In both groups the antibodies became detectable 3-6 weeks after transplantation but the titres were much higher following primary infection. IgM antibodies persisted throughout follow-up periods of up to 2 years after transplantation in some cases.

Antibodies, Viral↗
PubMed1982

Antibody against viruses in maternal and cord sera: specific antibody is concentrated on the fetal side of the circulation.

Paired maternal and cord sera from 100 pregnancies were tested for antibodies against herpes simplex virus, measles virus and respiratory syncytial virus by complement fixation and for antibodies against rubella virus, influenza A virus and influenza B virus by haemagglutination-inhibition. For four viruses (herpes simplex, measles, respiratory syncytial and rubella) higher levels of antibody were found in cord than in maternal sera. There was no difference between maternal and cord serum titres against influenza B virus but significantly higher levels of antibody against influenza A virus were found in maternal sera than in cord sera. This discrepancy was investigated by measuring antibodies against the surface antigens of influenza A by a complement fixation technique, and by single radial haemolysis. Both methods showed a preponderance of virus-specific antibody in cord sera. We conclude that IgG antibodies against most, if not all, viruses are concentrated on the fetal side of the circulation, but the conventional haemagglutination-inhibition techniques may fail to detect this difference.

Antibodies, Viral↗
PubMed1982

Infection with cytomegalovirus during pregnancy: specific IgM antibodies as a marker of recent primary infection.

Specific IgM antibodies that persisted for up to four months were detected by radioimmunoassay (RIA) in the sera of 16 (55%) of 29 women with primary infections due to cytomegalovirus (CMV). The RIA for IgM detected primary infections in six (86%) of seven sera obtained within four months of seroconversion. In contrast, IgM antibodies were never detected by RIA in 104 serum samples from 18 women with recurrent infections due to CMV, irrespective of whether intrauterine transmission of virus had occurred. Specific IgM antibodies were also detected in the earliest samples during pregnancy of serum from three (14%) of 21 women whose type of infection with CMV was unknown but who had been delivered of congenitally infected infants. All of these results show that primary infection with CMV in the first trimester of pregnancy can be diagnosed by testing a single serum sample by RIA for IgM antibodies. Attempts to measure IgM antibodies by immunofluorescence gave a high frequency (19 [18%] of 104) of false-positive reactions.

Antibodies, Viral↗
PubMed1982

Is post partum rubella vaccination worthwhile?

This study was designated to determine whether a program of screening for rubella antibodies during pregnancy, coupled with selective vaccination after delivery, could effectively increase herd immunity. One thousand women were studied when they returned for further antenatal care after having been screened, and possibly vaccinated, during an earlier pregnancy. Overall, the program was shown to be 83% effective since 108 women were truly seronegative in their initial pregnancies and 90 of them had been rendered immune by the time of their next pregnancy. The 18 failures of the program were attributed to the haemagglutination inhibition test employed (eight cases), failure to administer vaccine (seven cases) and true vaccine failures (three cases). Five pregnant women became infected with rubella virus during the study but all were in their initial pregnancies. All seronegative women were shown to follow the instruction not to become pregnant within three months of vaccination. We conclude that a program of screening for immunity, together with selective vaccination post partum, can significantly reduce both the number of susceptible women and the number who experience rubella infection during pregnancy. Such programs should be vigorously encouraged as a means of helping to prevent congenital rubella.

Antibodies, Viral↗